Eosinophilic Esophagitis
Conditions
Keywords
Eosinophilic esophagitis, acid reflux
Brief summary
The purpose of this study is to assess the clinical efficacy of proton pump inhibitors in comparison to aerosolized swallowed steroids for the treatment of eosinophilic esophagitis (EE). EE is an increasingly recognized disorder that has been associated with dysphagia and food impaction. The presence of anatomical abnormalities in the esophagus such as longitudinal furrows, corrugated rings and a narrow caliber esophagus with friable mucosa are classic endoscopic findings. Diagnosis is established with the histologic finding of large numbers (\> 15) of eosinophils per high power field. The underlying pathologic mechanism remains poorly understood but food allergies and aeroallergens have been implicated. It is well known that gastroesophageal reflux disease (GERD) may cause esophageal eosinophilia, but it is unclear whether a complex relationship exists between GERD and EE, as recent data suggests. Furthermore, a large number of patients with clinical presentations and endoscopic findings highly suggestive of EE which is confirmed on histology are responding favorably to proton pump inhibitors. The aims of the study are to (1) compare the clinical efficacy of aerosolized swallowed Fluticasone to Esomeprazole for the treatment of eosinophilic esophagitis, (2) determine whether proton pump inhibitors are effective in the treatment of eosinophilic esophagitis, (3) determine the number of patients with eosinophilic esophagitis that have coexisting gastroesophageal reflux disease, and (4) correlate change in eosinophil count to improvement in symptoms before and after therapy.
Interventions
DRUGSwallowed fluticasone
440 µg twice daily for 8 weeks
DRUGEsomeprazole
40 mg once daily for 8 weeks
Sponsors
Walter Reed Army Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with an established diagnosis of EE defined as \> 20 eosinophils/HPF in the setting of dysphagia or food impaction. * Males and females age \> 18 years of age. * Ability to undergo ambulatory pH monitoring. * DEERS (Defense Enrollment Eligibility Reporting System) eligible. * Willingness to take a one month holiday from a PPI or steroids if they have been prescribed this prior to enrollment. * Willingness to participate and have additional biopsies taken during endoscopy and answer a questionnaire.
Exclusion criteria
* Patients \< 18 years of age. * Inability to give consent. * Inability to undergo endoscopy or contraindications to endoscopy. Any medical condition or disorder (including drug allergies), which would preclude the use of conscious sedation or the ability to tolerate upper endoscopy. * Contraindications to proton pump inhibitors or steroids. * Inability to accurately fill out a short questionnaire. * Pregnant females. A urine beta human chorionic gonadotropin (BHCG) prior to endoscopy will be offered to all female patients of child bearing potential (exceptions include post-menopausal, hysterectomy or bilateral tubal ligation). Positive BHCG results will prevent enrollment. * Known coagulation abnormalities, thrombocytopenia and patients on coumadin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Responded | 8 weeks | Histologic resolution of esophageal eosinophilia. Response is defined as achieving \< 7 eosinophils/high power field in both the proximal and distal esophagus. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptom Score | 8 weeks | Using a validated questionnaire, symptoms will be assessed at baseline and following therapy. |
| Endoscopic Change | 8 weeks | Following therapy, resolution of EE findings will be assessed. |
Countries
United States
Participant flow
Recruitment details
Subjects with symptoms of esophageal dysfunction were recruited from the GI clinic of Walter Reed Army Medical Center. Recruitment dates were from 2008-2010.
Pre-assignment details
Subjects with a confirmed diagnosis of EE based on symptoms and tissue biopsies were offered enrollment.All subject underwent 24-hour pH studies to stratify GERD positive and GERD negative. A computer generated list of random numbers was then used to separate patients into two equal treatment groups (esomeprazole and fluticasone proprionate).
Participants by arm
| Arm | Count |
|---|---|
| Esomeprazole Esomeprazole : 40 mg once daily for 8 weeks | 21 |
| Swallowed Fluticasone Swallowed fluticasone : 440 µg twice daily for 8 weeks | 21 |
| Total | 42 |
Baseline characteristics
| Characteristic | Swallowed Fluticasone | Esomeprazole | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 21 Participants | 42 Participants |
| Age Continuous | 38 years STANDARD_DEVIATION 10 | 38 years STANDARD_DEVIATION 10 | 38 years STANDARD_DEVIATION 19 |
| Region of Enrollment United States | 21 participants | 21 participants | 42 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 19 Participants | 19 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 21 | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
Primary
Number of Participants Who Responded
Histologic resolution of esophageal eosinophilia. Response is defined as achieving \< 7 eosinophils/high power field in both the proximal and distal esophagus.
Time frame: 8 weeks
Population: Sample size estimation was based on the assumptions:10% of the EE patients will respond to PPI compared to 55% of patients treated with steroids. Controlling the probability of a Type I error at alpha=0.05, a sample of 38 patients in the treatment groups (19 in each arm) will have 80% power to detect a difference in treatment response of 45%.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Esomeprazole | Number of Participants Who Responded | 7 participants |
| Swallowed Fluticasone | Number of Participants Who Responded | 4 participants |
Secondary
Endoscopic Change
Following therapy, resolution of EE findings will be assessed.
Time frame: 8 weeks
Secondary
Symptom Score
Using a validated questionnaire, symptoms will be assessed at baseline and following therapy.
Time frame: 8 weeks